To date we have learned that specific microRNA's are altered by radiation in normal human fibroblasts. Experiments done to try and elucidate the mechanism for the change noted. We have shown that free radical formation due to radiation treatment may be responsible and this can be reversed by a free radical scavenger such as cysteine. In a mouse model, we induced fibrosis in one hind leg of mice using 35Gy of radiation in a single fraction and noted that microRNA's were altered in the radiation induced fibrotic leg as compared with the normal leg. In the upcoming year we will further investigate this mechanism and will be making a knockout mouse for a microRNA of interest to detemine if late toxicity from radiation may be reversed with a drug against microRNA's.